Cell growth, propagation, and development all require duplication and faithful segregation of chromosomal DNA. To ensure that these essential processes are proceeding normally, cells possess many regulatory mechanisms that couple division or development to the fidelity of chromosomal transmission. This proposal focuses on several aspects of the Bacillus subtilis cell cycle, including the mechanisms controlling chromosome orientation and partitioning, the spatial control of DNA replication, and the connections between cell cycle and the initiation of sporulation. The fundamental mechanisms controlling cell cycle, development, signal transduction, and gene expression are easily studied in B. subtilis with a combination of cell biological, genetic, molecular, physiological and biochemical approaches. Because many of the proteins involved in these processes are highly conserved in many organisms, the insights gained from this work are likely to be of broad relevance. Learning more about the essential mechanisms governing cell cycle could also lead to identification of new targets for antimicrobial therapy. The three main areas of interest include chromosome dynamics (orientation, structure and partitioning), spatial control of DNA replication, and the relationship between these processes and the initiation of sporulation. The investigator plans to: 1) determine whether the position of the origin of replication on the chromosome establishes overall orientation; 2) to characterize the movement of DNA through the polymerase; 3) to characterize the role of smc in chromosome dynamics; 4) to investigate the role of three genetic determinants SpoOJ, its binding site parS, and its negative regulator Soj in regulation of sporulation; and 5) to identify and characterize genes that couple initiation of sporulation to DNA replication.